The reversible chemical modification of deoxypolynucleotides and DNA with N-cyclohexyl-N'-Beta-(4-methylmorpholinium)ethylcarbodiimide p-toluenesulfonate will be studied. Experiments will be performed to determine the effect of this modification in restricting the action of various deoxyribonucleases. The expected increase in specificity of these enzymes caused by the modification of some of nucleotide bases will be exploited in methods designed to produce larger specific fragments for sequence analysis. Other modifications, such as the incorporation of polyhydroxy compounds at the monophosphate terminals of deoxypolynucleotides, will also be investigated. These modifications should permit the isolation of all fragments containing the terminal group from a particular enzymatic digestion, thus permitting the sequences of substantial regions near the terminals of DNA molecules to be analyzed.